JP2001026552A - Composition of external use preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject composition quickly affording moderate thermesthesia and improved in feeling as well when applied to the skin. SOLUTION: This composition comprises a thermesthesia-imparting substance and at least one kind of clay mineral comprising a phyllosilicate of the formula (1) or formula (2) described below; formula (1):[(Si8-yAly) (M(III)aM(II)bLic) O20(OH)4-xFx]n-.Az+n/z (M(III) is a trivalent metal ion; M(II) is a bivalent metal ion; A is an exchangeable cation; 0<=x<=4.0; 0<=y<=3.0; 0<=a<=5.0; 0<=b<=7.0; 0<=c<=2.5; 3<(a+b+c)<7; 0<n<=2.0; (z)is 1, 2 or 3), and formula (2): [Si8(MdqLis)O20Fz]Bs (B is lithium or sodium; 3.5<=p<=5.5; 0<=s<=3.0).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an external preparation composition which, when applied to the skin, quickly develops an appropriate warm feeling and is excellent in use feeling.

[0002]

2. Description of the Related Art Conventionally, an external preparation containing a nonsteroidal anti-inflammatory agent, which has been used as, for example, an anti-inflammatory or analgesic agent, has a problem in that an application site having inflammation is cold. It has been proposed to add a warming-imparting substance such as pepper extract in order to eliminate the feeling.

[0003] However, in order to quickly develop the warm sensation, it is necessary to blend a large amount of a warming substance. On the other hand, if a large amount of the warming substance is blended, there is a problem of skin irritation. Therefore, a technique for improving the usability at the time of application has been desired.

[0004] The present invention has been made in view of the above circumstances,
It is an object of the present invention to provide an external preparation composition that quickly develops a warm sensation when applied to the skin and has an excellent feeling upon use.

[0005]

Means for Solving the Problems and Embodiments of the Invention The present inventors have conducted intensive studies in order to achieve the above object, and as a result,
Clay minerals composed of layered silicates of a specific composition, such as montmorillonite, contain ions that are exchangeable with water molecules between the layers, and form other organic minerals such as forming organic complexes and swelling ability. Attention has been paid to having different properties, and when such clay minerals are combined with a warming-imparting substance, skin irritation can be suppressed even if the compounding amount may cause skin irritation conventionally. In addition, the present inventors have found that an appropriate warm feeling can be promptly felt at a site to be applied to the skin, and have accomplished the present invention.

[0006] That is, the present invention is characterized in that it comprises a warming substance and at least one or more clay minerals comprising a layered silicate represented by the following general formula (1) or (2). An external preparation composition is provided. _{[(Si 8-y Al y} ) (M (III) a M (II) b Li c) O 20 (OH) 4-x F x] n - · A z + n / z ··· (1) ( where Wherein M (III) is a trivalent metal ion;
(II) is a divalent metal ion, A is an exchangeable cation, x is a number satisfying the relationship 0 ≦ x ≦ 4.0, and y is 0 ≦
It is a number that satisfies the relationship y ≦ 3.0, and a, b, and c are
0 ≦ a ≦ 5.0, 0 ≦ b ≦ 7.0, 0 ≦ c ≦
2.5, a number satisfying the relationship of 3 <(a + b + c) <7,
n is a number satisfying 0 <n ≦ 2.0, and z is 1, 2 or 3. _{) [Si 8 (Mg p Li} s) O 20 F 2] B s ··· (2) ( where, the formula B is lithium or sodium,
p is a number satisfying the relationship of 3.5 ≦ p ≦ 5.5, and s is 0 ≦
This is a number that satisfies the relationship of s ≦ 3.0. )

Hereinafter, the present invention will be described in more detail. The external preparation composition of the present invention comprises a warming substance and a clay mineral comprising a layered silicate represented by the above general formula (1) or (2). By doing so, when applied to the skin, a warm sensation is quickly developed, the skin is not irritating, and the feeling of use is excellent. Here, the substance for imparting warmth may be any substance that gives a warm feeling when applied to the skin,
Examples of such a warming substance include capsicoside, capsaicin, capsaicinoids, capsaicin analogs such as dihydroxycapsaicin, capsanthin, capsicum extract, capsicum extract, capsicum tincture, capsicum-derived capsicum-derived warming substances, benzyl nicotinate, and the like.
Examples include β-butoxyethyl nicotinic acid, N-acylvanillylamide, vanillylamide nonylate and the like, and these can be used alone or in an appropriate combination of two or more. In the case of the present invention, among these, capsicosides derived from capsicum, capsaicin analogs such as capsaicin and capsaicinoid, capsicum extract, capsicum tincture, capsicum powder and the like are particularly preferable.

The amount of the warming substance in the external preparation composition of the present invention is not particularly limited, but may be 0.0001 to 7% (% by weight, hereinafter the same) based on the whole composition. Preferably it is 0.001 to 5%, more preferably 0.01 to 3%. If the amount is too small, a sufficient warm feeling may not be obtained. If the amount is too large, it may be difficult to reduce skin irritation.

The external preparation composition of the present invention comprises at least one kind of clay mineral comprising a layered silicate represented by the following general formula (1) or the following general formula (2) together with the above warming substance. It is. _{[(Si 8-y Al y} ) (M (III) a M (II) b Li c) O 20 (OH) 4-x F x] n - · A z + n / z ··· (1) [Si _{8 (Mg p Li s) O} 20 F 2] B s ··· (2)

Here, in the general formula (1), M
(III) is a trivalent metal ion such as an aluminum ion, an iron ion, and a chromium ion, and M (II) is a magnesium ion, an iron ion, a nickel ion, a zinc ion, a cobalt ion, a cadmium ion, a copper ion,
It is a divalent metal ion such as manganese ion and lead ion.

In the above formula (1), A is an exchangeable cation, specifically, an alkali metal ion such as hydrogen ion, sodium ion, potassium ion or lithium ion, or an alkaline earth ion such as calcium or magnesium. Metal ions, metal ions other than these alkali metal ions and alkaline earth metal ions, such as monovalent metal ions such as silver ions, divalent metal ions such as zinc ions and iron ions, and trivalent metal ions such as aluminum ions Metal ions such as monoethanolamine,
Organic groups such as alkanolamine groups such as diethanolamine and triethanolamine, alkyl quaternary ammonium groups such as trimethylammonium and tetramethylammonium, and basic amino acid groups such as lysine and arginine are also included.

X is a number that satisfies the relationship 0 ≦ x ≦ 4.0, y is a number that satisfies the relationship 0 ≦ y ≦ 3.0,
a, b, and c are respectively 0 ≦ a ≦ 5.0 and 0 ≦ b ≦ 7.
A number satisfying the relationship of 0, 0 ≦ c ≦ 2.5, 3 <(a + b + c) <7, and n is a number satisfying 0 <n ≦ 2.0;
z is 1, 2 or 3.

Specific examples of the clay mineral comprising a layered silicate represented by the above formula (1) include smectite clay minerals such as bentonite, montmorillonite, beidellite, nontronite, saponite, hectorite, sauconite, and stevensite. These can be used alone or in combination of two or more.

Such smectite clay minerals are naturally produced, for example, as products containing montmorillonite, such as Bentonite W, Wenger, Kunimine Kogyo from Kunimine Kogyo Co., Ltd.
And hectorite such as Vegum T, Vegum HV, Vegum F and Vegum K from Vanderbild as products containing saponite, such as Kunipia F, Western Bond from American Colloid Co., and Yellowstone from Dresser Minerals. Commercially available products include Hectabrite AW, Hectabrite 200 and Benton EW from American Colloid Co., Ltd., and Macaroid, etc. from National Reed. In addition, various types of synthetic smectite clay minerals are also sold. Ionite H is available from Mizusawa Chemical Industry Co., Ltd., Lucentite SWN, SAN is available from Corp Chemical Co., Ltd., and Laponite is available from Laporte Industries.

As the smectite clay mineral, an alkali-treated acid clay can be used.
That is, the acidic clay is usually defined as a 1% aqueous dispersion having a pH of 5 to 6 or less, a swelling degree of 10 ml / 2 g or less, and a content of SiO ₂ and Al ₂ O _{3 in} a molar ratio of SiO ₂ / Al ₂ O. ₃ = 6 ~
No. 10 are named, such as acid clay from Nakajo, Koto, Kamikatani, Itoigawa, Niigata Prefecture, Mizusawa from Yamagata Prefecture, Kawasaki, Matsune, Kamikatani, Mikawa, Ome, Kamisami Fuller's earth from the United Kingdom and Fl from the United States showing similar properties to these acid clays in addition to acid clay from the United States
oride earth, Warkel e from Germany
rde and the like. Exchangeable cations present in acid clay include sodium ions, potassium ions,
There are magnesium ion, iron ion, calcium ion, aluminum ion and the like. These acidic clays can be blended in the same manner as the smectite-based clay mineral by alkali treatment.

Here, in the case of the present invention, the smectite-based clay mineral has an average particle size of 10 to 5000 nm measured by a dynamic light scattering method and an absolute value of ζ potential measured by an electrophoretic light scattering method. It is preferable to use one having a purity of 30 mV or more and a purity of 90% or more determined by a powder X-ray diffraction method. If the average particle size of the primary fine particles of the clay mineral is too small, a large amount of clay mineral may be required to thicken the external preparation composition, while the average particle size of the primary particles is stable when the average particle size is too large. A dispersed state may not be obtained. On the other hand, when the absolute value of the ζ potential is less than 30 mV, the clay mineral particles tend to be easily condensed, and agglomerates may be settled during the production of the external preparation composition, so that the dispersion stability may be reduced. Further, if the purity is too low, a sufficient thickening effect may not be obtained.

Next, another clay mineral of the present invention is a clay mineral comprising a layered silicate represented by the following general formula (2). In _{[Si 8 (Mg p Li s} ) O 20 F 2] B s ··· (2) the formula (2), B is lithium or sodium, p is the relationship of 3.5 ≦ p ≦ 5.5 A number that satisfies
Is a number that satisfies the relationship 0 ≦ s ≦ 3.0.

Specific examples of the clay mineral comprising the layered silicate represented by the above formula (2) include Somasif manufactured by Corp Chemical Co., Ltd., and DP-DM or DM Clean manufactured by Topy Industries, Ltd. Can be used alone or in an appropriate combination of two or more.

The amount of the clay mineral in the external preparation composition of the present invention (the total amount when two or more types are mixed) is not particularly limited and can be appropriately selected. The compounding ratio (weight ratio) to the substance is
Warm sensation imparting substance: Clay mineral = 0.00001: 1 to 5:
1, preferably 0.0001: 1 to 3: 1, more preferably 0.0003: 1 to 2: 1. If the proportion of the clay mineral is too low, it may be difficult to sufficiently obtain the effects intended by the present invention, and if the proportion of the clay mineral is too high, not only the effect due to further blending is not obtained, There may be restrictions on formulation design. The amount of the clay mineral is 0.1% based on the whole composition.
It is suitable that the content is 01 to 10%, preferably 0.01 to 7%, more preferably 0.01 to 5%.

The external preparation composition of the present invention may further contain a pharmaceutically active ingredient such as a nonsteroidal anti-inflammatory agent.
Here, the kind of the above-mentioned medicinal component is not particularly limited as long as it can be blended with the external preparation for skin.

Specific examples of the above-mentioned active ingredients include actinomycin D, acrinol, adipiodone, piperazine adipate, aspirin, acetylkitasamycin,
Acetyl spiramycin, acemethacin, amidotrizoic acid, ethyl aminobenzoate, amphotericin B, amoxicillin, alclofenac, alprostadil alphadex, benzoic acid, estradiol benzoate, sodium benzoate, ampicillin, iotaramic acid, itroxic acid, iopanoic acid, iophanic acid Podart sodium, L-
Isoleucine, ibuprofen, indomethacin, ursodesoxycholic acid, ethacrynic acid, quinine ethyl carbonate, testosterone enacinate, fluphenazine enanthate, metenolone enanthate, enoxacin, acetylcholine chloride for injection, suxamethonium chloride, bethanechol chloride, aclarubicin hydrochloride, arginine hydrochloride , Ethyl cysteine hydrochloride, oxybuprocaine hydrochloride, cocaine hydrochloride, cyclopentolate hydrochloride, dilazep hydrochloride, diltiazem hydrochloride, cetraxiad hydrochloride, cefotiam hydrochloride,
Cefmenoxime hydrochloride, thalassopicillin hydrochloride, tetracaine hydrochloride, todralazine hydrochloride, nicardipine hydrochloride, bacampicillin hydrochloride, pivmecillinam hydrochloride, flavoxate hydrochloride, procaine hydrochloride, pethidine hydrochloride, meclofenoxate hydrochloride, moxycilitate hydrochloride, lysine hydrochloride, oxaprozin, kainic acid, carbamic acid Chlorphenesin, carbidopa, carbenicillin sodium, L-carbocysteine, potassium canrenoate, valerium betamethasone, sodium gold thiomalate, citric acid, sodium citrate, fentanyl citrate, potassium pentoxyberinklabranate, glycyrrhetinic acid , Clinofibrate, calcium gluconate, cloxacillin sodium, clofibrate, cromoglycic acid, sodium cromoglycate, Toprofen, tocopherol calcium succinate, hydrocortisone succinate, prednisolone succinate, guanabens acetate, chlormadinone acetate, cortisone acetate, tocopherol acetate, hydrocortisone acetate, prednisolone acetate, sidecademycin acetate, metenolone acetate, retinol acetate, sazapyrine, salazosyl pyridine , Glycol salicylate, sodium salicylate, physostigmine salicylate, methyl salicylate, cyclacillin, cyclandate, dicloxacillin sodium, diclofenac,
Diclofenac sodium, dinoprost, diflunisal, betamethasone dipropionate, ipratropium bromide, distigmine bromide, scopolamine hydrobromide, homatropine hydrobromide, pyridostigmine bromide, butyl scopolamine bromide, butropium bromide, propantherin bromide, Methyl benactidium bromide, mepenzolate bromide,
Ifenprodil tartrate, protilesone tartrate, levallorphan tartrate, simfibrate, G-strophantin, suprofen, sulindac, sulbenicillin sodium, cefaclor, cefazoline sodium, cefatridine propylene glycol, cefadroxil,
Cefapirin sodium, cefamandole sodium, cephalexin, cephalotin sodium, cephaloridine, cefoxitin sodium, cefotaxime sodium, cefotetan, cefoperazone sodium, cefsulodin sodium, ceftizoxime sodium, cefpyramid sodium, cefbupera Zon sodium, cefmetazole sodium, cefradine, cefloxazine, thiaprofenic acid, ticarcillin sodium,
Dehydrocholic acid, tranexamic acid, tryptophan,
Tolfenamic acid, L-threonine, trepivton, naproxen, nalidixic acid, nicotinic acid, nicomol, niceritrol, nifedipine, baclofen, pyrantel pamoate, calcium paraaminosalicylate, L-valine, sodium valproate, retinol palmitate,
Calcium pantothenate, bisacodyl, pipemidic acid trihydrate, piperacillin sodium, tipepidine hibenzate, pyrenxin, piroxicam, L-phenylalanine, phenoxymethylpenicillin potassium, felbinac, fentiazac, fenbufen, clemastine fumarate, brovincamine fumarate, benzicran fumarate , Formoterol fumarate, bumetanide, pranoprofen, fluocinonide, sodium fluorescein, flufenamic acid, flurbiprofen, floctafenin, proglumide, furosemide, protidic acid, testosterone propionate, josamycin propionate, drostanolone propionate, beclomethasone propionate , Probenecid, sodium heparin, potassium benzylpenicillin Calcium folinate, mitomycin C, ergometrine maleate, chlorpheniramine maleate, prochlorperazine maleate, Purufenajin maleic acid, ergometrine maleate,
Levomepromazine maleate, Midecamycin, Gabexate mesylate, Camostat mesylate, Methiazic acid, L-methionine, Methyldopa, Neostigmine methylsulfate, Methotrexate, Mefenamic acid, Melphalan, Folic acid, Iodamide, Hydrocortisone butyrate, Latamoxef sodium, Rameside, Riome Examples include, but are not limited to, thyronine sodium, rifampicin, atropine sulfate, vincristine sulfate, bleomycin sulfate, peplomycin sulfate, polymyxin B sulfate, reserpine, levothyrosine sodium, levodopa, L-leucine, loxoprofen, loxoprofen sodium and the like. Not something. These drugs can be used alone or in an appropriate combination of two or more.

In the case of the present invention, among the above-mentioned medicinal components, in particular, drugs which are usually regarded as effective components for skin diseases and / or care such as anti-inflammatory analgesics, anti-inflammatory agents, keratolytic agents, for example, tolfenamic acid, mefenam Acid, flufenamic acid, salicylic acid, aspirin, sazapyrine, alclofenac,
Diclofenac sodium, suprofen, loxoprofen sodium, ibuprofen, naproxen, flurbiprofen, ketoprofen, fenbufen,
Glycyrrhetinic acid, indomethacin, acemethacin, methiazinic acid, protidic acid, sulindac, pranoprofen, fenthiazac, diflunisal, thiaprofenic acid, oxaprozin, piroxicam, sodium cromoglycate, felbinac, etc. Particularly preferred are profen, felbinac, diclofenac sodium, sodium cromoglycate and the like, with indomethacin being most preferably used.

The amount of the above-mentioned medicinal component in the whole external preparation composition of the present invention is not particularly limited, and can be appropriately selected depending on the type of the external preparation composition, the purpose of use, and the like. 0.01 to 10%, more preferably 0.1 to 7%, even more preferably 0.1 to 5% of the whole product
Is preferred. If the amount of the above-mentioned medicinal components is too small, sufficient medicinal effects may not be obtained in some cases. If the amount is too large, problems such as skin irritation may occur.

The external preparation composition of the present invention is not particularly limited in its dosage form. For example, various types of skin prepared into dosage forms such as a patch base, a lotion, a gel (gel), etc. It can be prepared as an external preparation, and is particularly suitable as a patch base. When using the external preparation composition of the present invention as a patch base, a patch can be obtained by applying the patch base to a support.In this case, an adhesive used for the patch base is, It is sufficient that the adhesive has an adhesive force that can fix the patch on the skin surface at normal temperature for a long time, and is not particularly limited. For example, an aqueous adhesive, an acrylic adhesive, a rubber adhesive, a silicone resin adhesive, or the like can be used.

When prepared as an aqueous pressure-sensitive adhesive, the composition is not particularly limited, and any composition can be used.
Polyacrylic acid, polyacrylate, polyvinyl alcohol, polyvinylpyrrolidone, polyvinylpyrrolidone
Vinyl acetate copolymer, carboxyvinyl copolymer, methylcellulose, carboxymethylcellulose,
Carboxymethyl cellulose salt, hydroxypropyl cellulose, sodium alginate, gelatin, pectin, polyethylene oxide, methyl vinyl ether
One or more water-soluble polymer substances such as maleic anhydride copolymer and carboxymethyl starch (1 to 15% of the total amount of the base, usually mixed), kaolin, titanium oxide, zinc oxide, aluminum hydroxide, One or more inorganic powders other than the clay minerals such as silicic anhydride (0 to 10% of the total amount of the base in general), propylene glycol, glycerin, sorbitol, sodium pyrrolidone carboxylate;
One or more humectants such as sodium lactate (mixing amount: usually 0 to 20% of the total amount of the base) and water mixed in an appropriate ratio can be used.

In this case, such an aqueous pressure-sensitive adhesive contains a metal ion-crosslinkable hydrogel base, particularly polyacrylic acid and / or polyacrylate, and further contains sodium carboxymethylcellulose and / or alkali metal alginate. A non-gelatin based base may be preferably used. That is, the hydrogel base of the above composition has a strong adhesive strength,
In addition, since the water content is high and the shape retention is excellent, the use of this water-containing gel base allows the effective ingredient to be efficiently absorbed into the skin when the above-mentioned drug is added thereto.

Here, any polyacrylic acid can be used, and the molecular weight and the shape such as linear or branched chain are not particularly limited, but those having a molecular weight of 10,000 to 10,000,000 are used. Are preferable, and particularly, the weight average molecular weight is 10,000 to less than 500,000, 500,000 to less than 2,000,000, and 2,000,000 to
It is preferable to combine two or more kinds of polyacrylic acid having an average molecular weight of 7,000,000 and a salt thereof, since the feeling in use is improved. In addition, in addition to a polymer obtained by polymerizing ordinary acrylic acid, a carboxyvinyl polymer, for example, a partially crosslinked acrylic acid polymer such as Carpopol (trade name: manufactured by Goodrich Corporation in the United States) is also preferably used. Can be used.

Examples of polyacrylates include monovalent metal salts of polyacrylic acid such as sodium polyacrylate and potassium polyacrylate, monoethanolamine polyacrylate, diethanolamine polyacrylate, triethanolamine polyacrylate and the like. One or two of amine salt of polyacrylic acid, ammonium salt of polyacrylic acid, etc.
More than one species may be suitably used.

The hydrogel base having the above composition can obtain a base having an arbitrary pH by changing the mixing ratio of polyacrylic acid and polyacrylate. In this case, The mixing ratio of polyacrylic acid and polyacrylate is preferably 1:10 to 10: 1, and the weight of polyacrylic acid is 1/1 of the weight of polyacrylate.
If it is less than 10, sufficient adhesion to the skin may not be obtained, and if the weight of polyacrylic acid is more than 10/1 of the weight of polyacrylate, sufficient thickening will not be performed and the plaster will sag. Cases arise. Further, when the water-containing gel base comprising the above components is metal-crosslinked with a polyvalent metal salt, examples of the polyvalent metal salt include calcium chloride, magnesium chloride, aluminum chloride, potassium alum, ammonium alum, iron alum, aluminum sulfate, and sulfate sulfate. Ferrous iron, magnesium sulfate, EDTA (ethylenediaminetetraacetic acid)
Soluble salts such as calcium, EDTA-aluminum, EDTA-magnesium, stannous chloride, calcium hydroxide, ferric hydroxide, aluminum hydroxide, calcium carbonate, magnesium carbonate, calcium phosphate, magnesium stearate, aluminum stearate, Calcium citrate, barium sulfate, barium hydroxide, aluminum allantoinate, aluminum acetate, aluminum glycinate, synthetic hydrotalcite, magnesium metasilicate aluminate, magnesium aluminate silicate, stannous hydroxide, α-stannic acid One or more selected from sparingly soluble or poorly soluble salts, and the like, and a chelating or dispersing agent for metal ions such as sodium EDTA-2, citric acid, tartaric acid, urea, and ammonia as a crosslinking speed regulator. Competent Organic acids, organic acid salts, may be formulated and organic bases.

In the acrylic pressure-sensitive adhesive, the (co) polymer of an alkyl (meth) acrylate obtained from an aliphatic alcohol having 4 to 18 carbon atoms and (meth) acrylic acid, A copolymer of the above-mentioned alkyl (meth) acrylate and other functional monomers is preferably used.

Examples of the (meth) acrylate include butyl acrylate, isobutyl acrylate, hexyl acrylate, octyl acrylate, 2-ethylhexyl acrylate, isooctyl acrylate, decyl acrylate, isodecyl acrylate, lauryl acrylate. , Stearyl acrylate, methyl methacrylate, butyl methacrylate, isobutyl methacrylate, 2-methacrylic acid
Examples include ethylhexyl, isooctyl methacrylate, isodecyl methacrylate, lauryl methacrylate, and stearyl methacrylate. Examples of the functional monomer include a monomer having a hydroxyl group, a monomer having a carboxyl group, a monomer having an amide group, and a monomer having an amino group. Examples of the monomer having a hydroxyl group include hydroxyalkyl (meth) acrylates such as 2-hydroxyethyl (meth) acrylate and hydroxypropyl (meth) acrylate. Examples of the monomer having a carboxyl group include α, β unsaturated carboxylic acids such as acrylic acid and methacrylic acid, monoalkyl maleates such as butyl maleate, maleic acid, fumaric acid, crotonic acid and the like. Maleic anhydride also provides the same (co) polymerization component as maleic acid. Examples of the monomer having an amide group include alkyl (meth) acrylamides such as acrylamide, dimethylacrylamide, and diethylacrylamide; butoxymethylacrylamide,
Examples include alkyl ether methylol (meth) acrylamide such as ethoxymethylacrylamide, diacetone acrylamide, and vinylpyrrolidone. Examples of the monomer having an amino group include dimethylaminoacrylate. Other copolymerizable monomers and vinyl acetate,
Examples thereof include styrene, α-methylstyrene, vinyl chloride, acrylotrile, ethylene, propylene, and butadiene, and these may be copolymerized. The pressure-sensitive adhesive preferably contains 30% or more of (meth) acrylic acid alkyl ester as a (co) polymerization component.

As the rubber-based pressure-sensitive adhesive, natural rubber, synthetic isoprene rubber, polyisobutylene, polyvinyl ether, polyurethane, polybutadiene, styrene-butadiene copolymer, styrene-isoprene copolymer and the like are used. As the silicone resin-based pressure-sensitive adhesive, silicone rubber such as polyorganosiloxane is used.

Further, when the external preparation composition of the present invention is used as an adhesive base, in addition to the above-mentioned components, various compounding agents such as rosin-based resin, polyterpene resin, etc.
Coumarone-indene resin, petroleum resin, tackifier such as terpene phenol resin, liquid polybutene, mineral oil, lanolin, liquid polyisoprene, liquid polyacrylate,
Plasticizers such as latex, various polyvalent metal salts as cross-linking gelling agents, organic cross-linking agents such as dialdehyde starch, liquid paraffin, vegetable oil,
Appropriate components such as lard, beef tallow, higher alcohols, higher fatty acids, and activators can be blended.

As a support of the above-mentioned patch base, a support usually used for a patch is used. Materials for such a support include cellulose acetate, ethyl cellulose, polyethylene terephthalate, vinyl acetate-vinyl chloride copolymer, nylon, ethylene-vinyl acetate copolymer, plasticized polyvinyl chloride, polyurethane, polyethylene, polyvinylidene chloride. , Aluminum and the like. These are used, for example, as a single-layer sheet (film) or a laminate of two or more sheets (laminate). Materials other than aluminum may be used as a woven or nonwoven fabric.

As long as the effects of the present invention are not impaired, the external preparation composition of the present invention may further contain water-soluble components, preservatives, pH adjusters, and thickeners which are usually blended in various dosage forms in addition to the above essential components. Agents, antioxidants, dyes, fragrances, and the like can be appropriately added as necessary.

The preparation method is not particularly limited, and it can be prepared according to a conventional method of various dosage forms. For example, when used as an aqueous cataplasm, the above components are kneaded into a paste. It is obtained by preparing, applying this to the above-mentioned support and, if necessary, coating facing such as a polyethylene film. Further, for example, in the case of an acrylic, rubber, or silicone-based pressure-sensitive adhesive composition, a pressure-sensitive adhesive layer containing the warming substance and the clay mineral is formed on the surface of the support to obtain a patch. In order to form the pressure-sensitive adhesive layer, various coating methods such as a solvent coating method, a hot melt coating method, and an electron beam emulsion coating method can be used.

Further, in the case of liquid preparations such as ointments and lotions, a solvent as a base, an oil component, glycols, a surfactant, a water-soluble polymer compound and the like can be blended. , As a solvent, for example, water, ethanol, propyl alcohol, isopropyl alcohol,
As oil components such as acetone and benzyl alcohol, for example, lanolin, hydrogenated oil, lecithin, plastibase, liquid paraffin, oleic acid, stearic acid, myristic acid, palmitic acid, beeswax, paraffin wax, microcrystalline wax, diisopropyl adipate, myristic acid Isopropyl, isopropyl sebacate, isopropyl palmitate, squalane, squalene, cetanol, stearyl alcohol, oleyl alcohol, hexadecyl alcohol, silicone oil, etc., and glycols such as glycerin, propylene glycol, polyethylene glycol, polypropylene glycol, etc. For example, polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene alkyl ether Polyoxyalkylene alkyl ethers, such as polyoxyalkylene alkyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene glycol fatty acid ester, polyoxyethylene glycol ether, polyoxyethylene alkyl phenyl ether, Polyoxyethylene phytosterol, sorbitan fatty acid ester, glycerin fatty acid ester, etc.
Examples of the water-soluble polymer compound include carboxyvinyl polymer, sodium carboxymethylcellulose, polyvinyl alcohol, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, hydroxypropylmethylcellulose, and polyacrylic acid.

When prepared as an ointment or liquid, it can be produced by a conventional method. In the case of an ointment, for example, it can be prepared by sequentially adding the above-mentioned components to the above solvent and kneading for an appropriate time. If so, for example, it can be prepared by sequentially adding and dissolving each of the above components to the above solvent.

In the case of a gel, a gelling agent such as carboxyvinyl polymer and glycerin monooleate can be added in addition to the optional components of the above-mentioned liquid. For example, it can be prepared by sequentially adding and dissolving each of the above components other than the gelling agent to the above solvent, and then adding the gelling agent to cause gelation.

Further, other external preparation compositions can be produced by a usual method using components according to the kind.

The amount and method of use of the external preparation composition of the present invention are not particularly limited, and may be the same as those of the above-mentioned external preparations containing the above-mentioned medicinal components according to the dosage form of the external preparation composition. By applying and rubbing on the skin, an appropriate warm feeling can be quickly felt at the application site, and there is no problem with skin irritation and the feeling of use is excellent.

[0042]

According to the present invention, an appropriate warm feeling due to a warming substance can be quickly felt and the skin irritation is alleviated. An external preparation composition excellent in use feeling is obtained.

[0043]

EXAMPLES The present invention will be described below in detail with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples.

Examples 1 to 10, Comparative Examples 1 to 10
And the respective components shown in Table 2 were mixed and stirred by a Henschel mixer according to a conventional method to obtain Examples 1 to 10 and Comparative Examples 1 to 1.
No. 0 patch base was prepared. 100g of each base on non-woven fabric
/ M ² , and the polyethylene film was faced to produce a patch. Each patch was evaluated for warmth and skin irritation by the following methods. The results are shown in Tables 1 and 2.

<Evaluation of thermal sensation> Each patch was applied to the shoulders of 20 healthy persons (panelers) and 3 hours after the patch was applied to the skin.
The warm feeling after 0 minutes was sensory-evaluated for each panelist based on the following evaluation criteria, and the average score of each panelist was calculated. <Evaluation Criteria> 0: No feeling of warmth 1: Feeling of warmth but extremely weak 2: Feeling of weak warmth 3: Feel warmth 4: Clearly feel warmth 5: Feel strong warmth 6: I feel so warm that it hurts

<Skin Irritation Test> Male rabbits were subjected to the test. Prior to the administration of the sample, a rabbit having a good health condition was selected, and the back was shaved with a hair clipper, and 10 were selected as animals to be used.

The sample was cut into a size of 2.5 × 2.5 cm, attached to the depilated back of a rabbit, and the specimen was removed 24 hours later.

The skin reaction was observed 24 hours after removing the specimen.
Went after hours. In the judgment, a score was given according to the following criterion, and an average value was calculated. When the average point of skin irritation was 4.0 or more, the feeling of use was judged to be good.

[0049]

[0050]

[Table 1]

[0051]

[Table 2]

[Examples 11 to 20, Comparative Examples 11 to 20]
Example 1 was obtained by a conventional method using the components shown in Tables 3 and 4.
Creams of Nos. 1 to 20 and Comparative Examples 11 to 20 were prepared. Normal dosage of each cream is 20 healthy people (paneler)
Was applied to the shoulder of the sample, and the sensory evaluation of the warm feeling 30 minutes after the application was performed in the same manner as described above. Also, 100 μl of each cream was collected and dropped on a filter paper of a fin chamber (manufactured by Taisho Pharmaceutical Co., Ltd.), and attached to the depilated back of a rabbit. After 24 hours, it was removed and the application site was gently washed with water soaked cotton. The skin reaction was observed 24 hours after washing, and the skin irritation was evaluated in the same manner as described above. The results are shown in Tables 3 and 4.

[0053]

[Table 3]

[0054]

[Table 4]

[Examples 21 to 30, Comparative Examples 21 to 30]
Example 2 was obtained by a conventional method using the components shown in Tables 5 and 6.
Gels of Nos. 1 to 30 and Comparative Examples 21 to 30 were prepared. Each gel was evaluated for warmth and skin irritation in the same manner as described above. The results are shown in Tables 5 and 6.

[0056]

[Table 5]

[0057]

[Table 6]

[Examples 31 to 40, Comparative Examples 31 to 40]
Example 3 was carried out in a conventional manner using the components shown in Tables 7 and 8.
The lotions of 1 to 40 and Comparative Examples 31 to 40 were prepared. Each lotion was evaluated for warmth and skin irritation in the same manner as described above. The results are shown in Tables 7 and 8.

[0059]

[Table 7]

[0060]

[Table 8]

[Examples 41 to 50, Comparative Examples 41 to 50]
Ointments of Examples 41 to 50 and Comparative Examples 41 to 50 were prepared by a conventional method using the components shown in Tables 9 and 10.
The warmth and skin irritation of each ointment were evaluated in the same manner as described above. The results are shown in Tables 9 and 10.

[0062]

[Table 9]

[0063]

[Table 10]

Continued on the front page F term (reference) 4C076 AA07 AA09 AA72 BB31 CC05 DD09 DD27 DD29 DD34 DD38 DD46 DD49 DD50 DD51 DD70 EE06 EE09 EE23 EE32 EE53 EE58 FF70

Claims (1)

[Claims] An external preparation comprising a warming substance and at least one or more clay minerals comprising a layered silicate represented by the following general formula (1) or (2): Composition. _{[(Si 8-y Al y} ) (M (III) a M (II) b Li c) O 20 (OH) 4-x F x] n - · A z + n / z ··· (1) ( where Wherein M (III) is a trivalent metal ion;
(II) is a divalent metal ion, A is an exchangeable cation, x is a number satisfying the relationship 0 ≦ x ≦ 4.0, and y is 0 ≦
It is a number that satisfies the relationship y ≦ 3.0, and a, b, and c are
0 ≦ a ≦ 5.0, 0 ≦ b ≦ 7.0, 0 ≦ c ≦
2.5, a number satisfying the relationship of 3 <(a + b + c) <7,
n is a number satisfying 0 <n ≦ 2.0, and z is 1, 2 or 3. _{) [Si 8 (Mg p Li} s) O 20 F 2] B s ··· (2) ( where, the formula B is lithium or sodium,
p is a number satisfying the relationship of 3.5 ≦ p ≦ 5.5, and s is 0 ≦
This is a number that satisfies the relationship of s ≦ 3.0. )